FP802
FP802 is an orally active potent TwinF interface inhibitor that disrupts and detoxifies the NMDAR/TRPM4 death complex. FP802 exerts powerful neuroprotective effects in the 5xFAD mouse model of Alzheimer’s disease (AD) by preventing cognitive decline, preserving neuronal structural integrity, reducing amyloid-β plaque formation, and mitigating mitochondrial pathology. FP802 stops loss of motor neurons, reduces serum neurofilament light chain (NfL) levels, improves motor performance, and extends life in a mouse model of amyotrophic lateral sclerosis (ALS). FP802 can be used for AD and ALS research.
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- No. CAS: 61694-81-3
- Fòrmula: C11H17ClN2
- Peso molecular:212.72
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
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Actividad biológica
FP802 (8 μM, 24-72 h) disrupts the NMDAR/TRPM4 complex and provides neuroprotection in cellular models, without directly affecting neurite outgrowth[1].
FP802 (10 μM, 30 min) exhibits potent neuroprotection against glutamate (20 μM)-mediated toxicity (IC50 = 8.7 µM) and restores NMDA-suppressed immediate-early gene expression to physiological levels[2].
FP802 shows no antagonistic activity against NMDARs in HEK293 cells (IC50 > 250 μM for both, GluN1/GluN2A and GluN1/GluN2B)[2].
FP802 (30 min) dose-dependently blocks NMDA-induced death of post-mitotic neurons in forebrain organoids derived from sporadic ALS patient Induced Pluripotent Stem Cells (iPSCs)[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:mouse cortical neurons
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Concentration:10 μM
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Incubation Time:30 min
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Result:Eliminated the transcriptional shut-off induced by eNMDARs and boosted the NMDA bath application-induced expression of the immediate-early genes (IEGs) Atf3, Arc, Bdnf, cFos, Inhibin beta A, and Npas4 to reach levels that were comparable to those achieved by Bicuculline (HY-N0219)-induced action potential bursting.
FP802 (40 mg/kg, s.c., daily from ~week 15 for 4 weeks) safely halts motor neuron degeneration and extends survival in ALS mice by targeting the NMDAR/TRPM4 complex[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:5xFAD transgenic mice and wild-type littermates[1]
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Dosage:10 and 40 mg/kg
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Administration:p.o., daily for 4 months
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Result:Showed no apparent adverse effects on the liver, kidney, or heart.
Reduced the complex formation of GluN2B with TRPM4 in the 5xFAD mice at both 10 and 40 mg/kg.
Reduced complex formation of GluN2A with TRPM4 at 40 mg/kg.
Significantly decreased the interaction between NMDAR and TRPM4 without affecting the total protein levels of GluN2A, GluN2B, or TRPM4.
Led to a significant increase in the time 5xFAD mice spent in the target quadrant and the frequency with which they crossed the platform's prior location at the dose of 40 mg/kg, compared to vehicle.
Increased the time 5xFAD mice spent exploring the novel object in the Novel Object Recognition (NOR) test and the displaced object in the Novel Location Recognition (NLR) test relative to vehicle treatment.
Prevented the shift of mitochondrial morphologies from normal to pathological phenotypes in both CA1 and CA3.
Effectively preserved dendritic trees in 5xFAD mice as compared to controls, as demonstrated by increased total dendritic length and numbers of crossings in the Sholl analysis.
Prevented the increase in the density of 'apparent orphaned synapses' in both stratum oriens (CA1 basal dendrites) and stratum radiatum (CA1 apical dendrites) of 5xFAD mice.
Prevented the loss of excitatory and inhibitory synapses and the associated structural deterioration of postsynaptic densities (PSD) in the basal and apical dendrites of CA1 neurons, thereby preserving synaptic integrity in 5xFAD mice.
Led to a 25-40% reduction in Aβ plaque load, significantly limiting plaque development without completely preventing its formation.
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Animal Model:Male SOD1G93A transgenic mice and wild-type littermates[2]
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Dosage:40 mg/kg
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Administration:s.c., daily from ~week 15 for 4 weeks
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Result:Disrupted he interaction of TRPM4 with the NMDAR subunit GluN2B in mice spinal cord.
Significantly better neurological scores and less body weight loss than vehicle-treated controls.
Significantly improved motor performance (increased total distance traveled and rearing frequency in the open field).
Significantly extended the lifespan of SOD1G93A mice (survival median increased from 151 to 164 days).
Preserved larger soma sizes of lumbar spinal motor neurons compared to the control group at week 19.
Significantly reduced serum NfL levels while showing no effect on spinal microglial response or EAAT2 expression.
Showed no adverse effects on liver, kidney, heart, or blood counts.
Chemical Information
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No. CAS 61694-81-3
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Peso molecular 212.72
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Fòrmula C11H17ClN2
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SMILES
CCN(CC1=CC(Cl)=CC=C1)CCN
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[1]. Yan J, et al. The NMDAR/TRPM4 death complex is a major promoter of disease progression in the 5xFAD mouse model of Alzheimer's disease. Mol Psychiatry. 2025 Aug 26. [Content Brief]
[2]. Yan J, et al. TwinF interface inhibitor FP802 stops loss of motor neurons and mitigates disease progression in a mouse model of ALS. Cell Rep Med. 2024 Feb 20;5(2):101413. [Content Brief]
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